The overall objectives of the proposed research are to determine whether adenosine plays a role in the local regulation of fetal blood flow in the human term placenta, and whether placental prostanoids and renin also contribute to the local regulation. The in vitro dual-perfused placental cotyledon preparation from human term placentas, as developed by Panigel, is to be used to determine the actions of adenosine, adenine nucleotides, prostaglandins and angiotensin II on the resistance of the fetal placental vascular bed and to determine the formation and release of these autacoids and renin by the placenta in response to ischemia. The possibility of linkage between the actions of the vasoactive autocoids will be determined by means of specific inhibitors of autacoid action and synthesis. Adenosine levels in freshly-delivered placentas will be measured by high pressure liquid chromatography so that placental adenosine content can be correlated with duration of labor in normal term placentas, in pre- and post-term placentas and in placentas associated with acute or chronic fetal distress, e.g. as in hypertension. Slices of human term placenta in which the adenine nucleotide pool is 14C-labelled will be used to correlate 14C-adenosine formation with the degree of hypoxic stimulus. The release of prostanoids and/or renin by in vitro placental vessel segments will also be correlated with hypoxic stimulus. It is expected that this integrated approach of assessing both vascular and biochemical responses of the placenta will lead to a better understanding of the control of fetal-placental blood flow in normal and abnormal conditions.